Mitochondrial respiration as a target for neuroprotection and cognitive enhancement

Biochemical Pharmacology

Volumn 88, Issue 4, 2014, Pages 584-593

  Gonzalez Lima, F ^a   Barksdale, Bryan R ^a   Rojas, Julio C ^b  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Alzheimer's disease; Brain energy metabolism; Ketogenesis; Low level light laser therapy; Methylene blue; Mild cognitive impairment

Indexed keywords

ANTIOXIDANT; KETONE BODY; METHYLENE BLUE;

AEROBIC METABOLISM; ALZHEIMER DISEASE; ANTIOXIDANT ACTIVITY; BIOENERGY; BRAIN METABOLISM; BRAIN MITOCHONDRION; COGNITIVE DEFECT; ENERGY METABOLISM; HUMAN; KETOGENESIS; KETOGENIC DIET; LOW DRUG DOSE; LOW LEVEL LASER THERAPY; MEMORY; MENTAL DISEASE; MITOCHONDRIAL RESPIRATION; NERVE DEGENERATION; NEUROLOGIC DISEASE; NEUROPHARMACOLOGY; NEUROPROTECTION; NONHUMAN; NUTRITION; PHOTOTHERAPY; PRIORITY JOURNAL; REVIEW; TRANSCRANIAL LOW LEVEL LASER THERAPY;

ALZHEIMER'S DISEASE; BRAIN ENERGY METABOLISM; KETOGENESIS; LOW-LEVEL LIGHT/LASER THERAPY; METHYLENE BLUE; MILD COGNITIVE IMPAIRMENT;

ALZHEIMER DISEASE; COGNITION; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; KETONE BODIES; LASER THERAPY; METHYLENE BLUE; MITOCHONDRIA;

EID: 84897954167     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2013.11.010     Document Type: Review

References (142)

1. D. Attwell, and S.B. Laughlin An energy budget for signaling in the grey matter of the brain J Cereb Blood Flow Metab 21 2001 1133 1145 (Pubitemid 32947479)
2. J.C. Skou The influence of some cations on an adenosine triphosphatase from peripheral nerves Biochim Biophys Acta 23 1957 394 401
3. M.T. Wong-Riley Cytochrome oxidase: an endogenous metabolic marker for neuronal activity Trends Neurosci 12 1989 94 101 (Pubitemid 19067056)
4. J.C. Rojas, and F. Gonzalez-Lima Mitochondrial optic neuropathy: in vivo model of neurodegeneration and neuroprotective strategies Eye Brain 2 2010 21 37
5. F. Gonzalez-Lima, J. Valla, and L. Jorandby Cytochrome oxidase inhibition in Alzheimer's disease F. Gonzalez-Lima, Cytochrome oxidase in neuronal metabolism and Alzheimer's disease 1998 Plenum Press New York 171 201
6. M.F. Beal, B.T. Hyman, and W. Koroshetz Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases Trends Neurosci 16 1993 125 131 (Pubitemid 23085467)
7. W.D. Parker Jr., S.J. Boyson, and J.K. Parks Abnormalities of the electron transport chain in idiopathic Parkinson's disease Ann Neurol 26 1989 719 723 (Pubitemid 20011004)
8. R.H. Swerdlow, and S.M.A. Khan Mitochondrial cascade hypothesis for sporadic Alzheimer's disease Med Hypotheses 63 2004 8 20 (Pubitemid 38887104)
9. D.C. Wallace Mitochondrial genetics: a paradigm for aging and degenerative diseases Science 256 1992 628 632
10. R.H. Swerdlow, J.M. Burns, and S.M. Khan The Alzheimer's disease mitochondrial cascade hypothesis: progress and perspectives Biochim Biophys Acta 2013
11. R. Henneberry Excitotoxicity as a consequence of impairment of energy metabolism: the energy-linked excitotoxic hypothesis M.F. Beal, Mitochondria and free radicals in neurodegenerative diseases 1997 Wiley-Liss New York, NY
12. H.K. Anandatheerthavarada, and L. Devi Amyloid precursor protein and mitochondrial dysfunction in Alzheimer's disease Neuroscientist 13 2007 626 638 (Pubitemid 350077307)
13. P.S. Whitton Inflammation as a causative factor in the aetiology of Parkinson's disease Br J Pharmacol 150 2007 963 976 (Pubitemid 46628616)
14. M.F. Beal Aging, energy, and oxidative stress in neurodegenerative diseases Ann Neurol 38 1995 357 366
15. D.F. Silva, J.E. Selfridge, J. Lu, E.L.N. Roy, and L. Hutfles et al. Bioenergetic flux, mitochondrial mass and mitochondrial morphology dynamics in AD and MCI cybrid cell lines Hum Mol Genet 22 2013 3931 3946
16. S.J. Kish, C. Bergeron, A. Rajput, S. Dozic, F. Mastrogiacomo, and L.J. Chang et al. Brain cytochrome oxidase in Alzheimer's disease J Neurochem 59 1992 776 779
17. W.D. Parker Jr., C.M. Filley, and J.K. Parks Cytochrome oxidase deficiency in Alzheimer's disease Neurology 40 1990 1302 1303 (Pubitemid 20244999)
18. J. Valla, J.D. Berndt, and F. Gonzalez-Lima Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration J Neurosci 21 2001 4923 4930 (Pubitemid 32565651)
19. J. Zhou, E.D. Gennatas, J.H. Kramer, B.L. Miller, and W.W. Seeley Predicting regional neurodegeneration from the healthy brain functional connectome Neuron 73 2012 1216 1227
20. L. Mosconi, R. Mistur, R. Switalski, M. Brys, L. Glodzik, and K. Rich et al. Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease Neurology 72 2009 513 520
21. R. Sperling, and K. Johnson Biomarkers of Alzheimer disease: current and future applications to diagnostic criteria Continuum (Minneap Minn) 19 2013 325 338
22. P. Borghammer Perfusion and metabolism imaging studies in Parkinson's disease Dan Med J 59 2012 B4466
23. H. Fujishiro, E. Iseki, K. Kasanuki, Y. Chiba, K. Ota, and N. Murayama et al. A follow up study of non-demented patients with primary visual cortical hypometabolism: Prodromal dementia with Lewy bodies J Neurol Sci 2013
24. H. Shin, M.H. Kim, S.J. Lee, K.H. Lee, M.J. Kim, and J.S. Kim et al. Decreased metabolism in the cerebral cortex in early-stage Huntington's disease: a possible biomarker of disease progression J Clin Neurol 9 2013 21 25
25. M.T. Lin, and M.F. Beal Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases Nature 443 2006 787 795 (Pubitemid 44622683)
26. J.C. Rojas, A.K. Bruchey, and F. Gonzalez-Lima Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue Prog Neurobiol 96 2012 32 45
27. R.O. Wright, W.J. Lewander, and A.D. Woolf Methemoglobinemia: etiology, pharmacology, and clinical management Ann Emerg Med 34 1999 646 656 (Pubitemid 29510918)
28. C. Peter, D. Hongwan, A. Kupfer, and B.H. Lauterburg Pharmacokinetics and organ distribution of intravenous and oral methylene blue Eur J Clin Pharmacol 56 2000 247 250 (Pubitemid 30456685)
29. M. Wainwright, and K.B. Crossley Methylene blue - a therapeutic dye for all seasons J Chemother 14 2002 431 443 (Pubitemid 35346989)
30. T.M. Visarius, J.W. Stucki, and B.H. Lauterburg Stimulation of respiration by methylene blue in rat liver mitochondria FEBS Lett 412 1997 157 160 (Pubitemid 27310021)
31. A. Scott, and F.E. Hunter Jr. Support of thyroxine-induced swelling of liver mitochondria by generation of high energy intermediates at any one of three sites in electron transport J Biol Chem 241 1966 1060 1066
32. A.K. Bruchey, and F. Gonzalez-Lima Behavioral, physiological and biochemical hormetic responses to the autoxidizable dye methylene blue Am J Pharm Toxicol 3 2008 72 79
33. X. Zhang, J.C. Rojas, and F. Gonzalez-Lima Methylene blue prevents neurodegeneration caused by rotenone in the retina Neurotox Res 9 2006 47 57
34. J.C. Rojas, J.M. John, J. Lee, and F. Gonzalez-Lima Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy Neurotox Res 15 2009 260 273
35. P.D. Riha, A.K. Bruchey, D.J. Echevarria, and F. Gonzalez-Lima Memory facilitation by methylene blue: dose-dependent effect on behavior and brain oxygen consumption Eur J Pharmacol 511 2005 151 158 (Pubitemid 40417721)
36. N.L. Callaway, P.D. Riha, A. Bruchey, Z. Munshi, and F. Gonzalez-Lima Methylene blue improves brain oxidative metabolism and memory retention in rats Pharmacol Biochem Behav 77 2004 175 181 (Pubitemid 38076994)
37. P.E. Lindahl, and K.E. Oberg The effect of rotenone on respiration and its point of attack Exp Cell Res 23 1961 228 237
38. J.C. Rojas, N. Simola, B.A. Kermath, J.R. Kane, T. Schallert, and F. Gonzalez-Lima Striatal neuroprotection with methylene blue Neuroscience 163 2009 877 889
39. M. Oz, D.E. Lorke, and G.A. Petroianu Methylene blue and Alzheimer's disease Biochem Pharmacol 78 2009 927 932
40. J.C. O'Leary 3rd, Q. Li, P. Marinec, L.J. Blair, E.E. Congdon, and A.G. Johnson et al. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden Mol Neurodegener 5 2010 45
41. D.X. Medina, A. Caccamo, and S. Oddo Methylene blue reduces abeta levels and rescues early cognitive deficit by increasing proteasome activity Brain Pathol 21 2011 140 149
42. A. Ishiwata, O. Sakayori, S. Minoshima, S. Mizumura, S. Kitamura, and Y. Katayama Preclinical evidence of Alzheimer changes in progressive mild cognitive impairment: a qualitative and quantitative SPECT study Acta Neurol Scand 114 2006 91 96 (Pubitemid 44034255)
43. E.M. Sontag, G.P. Lotz, N. Agrawal, A. Tran, R. Aron, and G. Yang et al. Methylene blue modulates huntingtin aggregation intermediates and is protective in Huntington's disease models J Neurosci 32 2012 11109 11119
44. G.D. Bittner, C.P. Keating, J.R. Kane, J.M. Britt, C.S. Spaeth, and J.D. Fan et al. Rapid, effective, and long-lasting behavioral recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves J Neurosci Res 90 2012 967 980
45. P.D. Riha, J.C. Rojas, and F. Gonzalez-Lima Beneficial network effects of methylene blue in an amnestic model Neuroimage 54 2011 2623 2634
46. S. Deiana, C.R. Harrington, C.M. Wischik, and G. Riedel Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine Psychopharmacology (Berl) 202 2009 53 65
47. N.L. Callaway, P. Riha, K. Wrubel, D. McCollum, and F. Gonzalez-Lima Methylene blue restores spatial memory retention impaired by an inhibitor of cytochrome oxidase in rats Neurosci Lett 332 2002 83 86 (Pubitemid 35217846)
48. K.M. Wrubel, P.D. Riha, M.A. Maldonado, D. McCollum, and F. Gonzalez-Lima The brain metabolic enhancer methylene blue improves discrimination learning in rats Pharmacol Biochem Behav 86 2007 712 717 (Pubitemid 46829326)
49. F. Gonzalez-Lima, and A.K. Bruchey Extinction memory improvement by the metabolic enhancer methylene blue Learn Mem 11 2004 633 640 (Pubitemid 39299715)
50. J. Martinez Jr., R.A. Jensen, B. Vasquez, T. McGuiness, and J.L. McGaugh Methylene blue alters retention of inhibitory avoidance responses Physiol Psychol 6 1978 387 390
51. S. Huang, F. Du, Y.Y. Shih, Q. Shen, F. Gonzalez-Lima, and T.Q. Duong Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia Neuroimage 72 2013 237 242
52. A.L. Lin, E. Poteet, F. Du, R.C. Gourav, R. Liu, and Y. Wen et al. Methylene blue as a cerebral metabolic and hemodynamic enhancer PLoS ONE 7 2012 e46585
53. I. Walter-Sack, J. Rengelshausen, H. Oberwittler, J. Burhenne, O. Mueller, and P. Meissner et al. High absolute bioavailability of methylene blue given as an aqueous oral formulation Eur J Clin Pharmacol 65 2009 179 189
54. M.G. Shah-Khan, J. Lovely, and A.C. Degnim Safety of methylene blue dye for lymphatic mapping in patients taking selective serotonin reuptake inhibitors Am J Surg 204 2012 798 799
55. G.J. Naylor, B. Martin, S.E. Hopwood, and Y. Watson A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis Biol Psychiatry 21 1986 915 920 (Pubitemid 16037297)
56. F. Gonzalez-Lima, J. Valla, and S. Matos-Collazo Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients Brain Res 752 1997 117 126 (Pubitemid 27143904)
57. J. Valla, L. Schneider, T. Niedzielko, K.D. Coon, R. Caselli, and M.N. Sabbagh et al. Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairment Mitochondrion 6 2006 323 330 (Pubitemid 44817367)
58. M.T. Wong-Riley, F. Nie, R.F. Hevner, and S. Liu Brain cytochrome oxidase: functional significance and bigenomic regulation in the CNS F. Gonzalez-Lima, Cytochrome oxidase in neuronal metabolism and Alzheimer's disease 1998 Plenum Press New York 1 53
59. S.S. Dhar, and M.T. Wong-Riley Coupling of energy metabolism and synaptic transmission at the transcriptional level: role of nuclear respiratory factor 1 in regulating both cytochrome c oxidase and NMDA glutamate receptor subunit genes J Neurosci 29 2009 483 492
60. R.O. Poyton, P.R. Castello, K.A. Ball, D.K. Woo, and N. Pan Mitochondria and hypoxic signaling: a new view Ann N Y Acad Sci 1177 2009 48 56
61. A. Busse, A. Hensel, U. Guhne, M.C. Angermeyer, and S.G. Riedel-Heller Mild cognitive impairment: long-term course of four clinical subtypes Neurology 67 2006 2176 2185 (Pubitemid 46035473)
62. J.C. Morris, M. Storandt, J.P. Miller, D.W. McKeel, J.L. Price, and E.H. Rubin et al. Mild cognitive impairment represents early-stage Alzheimer disease Arch Neurol 58 2001 397 405 (Pubitemid 32217456)
63. R.C. Petersen, G.E. Smith, S.C. Waring, R.J. Ivnik, E.G. Tangalos, and E. Kokmen Mild cognitive impairment: clinical characterization and outcome Arch Neurol 56 1999 303 308 (Pubitemid 29120227)
64. C.M. Wischik, P. Bentham, D.J. Wischik, and K.M. Seng Tau aggregation inhibitor (TAI) therapy with rember™ arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks Alzheimer's Dementia 4 2008 T167
65. C.M. Wischik, P.C. Edwards, R.Y. Lai, M. Roth, and C.R. Harrington Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines Proc Natl Acad Sci U S A 93 1996 11213 11218 (Pubitemid 26333144)
66. B. Moosmann, T. Skutella, K. Beyer, and C. Behl Protective activity of aromatic amines and imines against oxidative nerve cell death Biol Chem 382 2001 1601 1612 (Pubitemid 33107702)
67. J.C. Rojas, and F. Gonzalez-Lima Neurological and psychological applications of transcranial lasers and LEDs Biochem Pharmacol 86 2013 447 457
68. F. Chiaravalloti, L. Gross, K.H. Rieder, S.M. Stojkovic, A. Gourdon, and C. Joachim et al. A rack-and-pinion device at the molecular scale Nat Mater 6 2007 30 33 (Pubitemid 46041472)
69. L. Santana-Blank, E. Rodriguez-Santana, and K. Santana-Rodriguez Theoretic, experimental, clinical bases of the water oscillator hypothesis in near-infrared photobiomodulation Photomed Laser Surg 28 Suppl. 1 2010 S41 S52
70. M. Hamblin, and T. Demidova Mechanisms of low level light therapy Proc SPIE 6140 2006 1 12
71. T. Karu Mechanisms of low-power laser light action on cellular level Proc SPIE 4159 2000 1 17
72. T. Karu Mitochondrial mechanisms of photobiomodulation in context of new data about multiple roles of ATP Photomed Laser Surg 28 2010 159 160
73. T. Karu Molecular mechanisms of the therapeutic effect of low intensity laser radiation Lasers Life Sci 2 1988 53 74 (Pubitemid 18079270)
74. K.R. Byrnes, X. Wu, R.W. Waynant, I.K. Ilev, and J.J. Anders Low power laser irradiation alters gene expression of olfactory ensheathing cells in vitro Lasers Surg Med 37 2005 161 171 (Pubitemid 41266301)
75. Y. Wollman, and S. Rochkind In vitro cellular processes sprouting in cortex microexplants of adult rat brains induced by low power laser irradiation Neurol Res 20 1998 470 472 (Pubitemid 28304584)
76. M.T. Wong-Riley, X. Bai, E. Buchmann, and H.T. Whelan Light-emitting diode treatment reverses the effect of TTX on cytochrome oxidase in neurons Neuroreport 12 2001 3033 3037 (Pubitemid 32907000)
77. M.T. Wong-Riley, H.L. Liang, J.T. Eells, B. Chance, M.M. Henry, and E. Buchmann et al. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase J Biol Chem 280 2005 4761 4771 (Pubitemid 40288647)
78. J.C. Rojas, J. Lee, J.M. John, and F. Gonzalez-Lima Neuroprotective effects of near-infrared light in an in vivo model of mitochondrial optic neuropathy J Neurosci 28 2008 13511 13521
79. J.T. Eells, M.M. Henry, P. Summerfelt, M.T. Wong-Riley, E.V. Buchmann, and M. Kane et al. Therapeutic photobiomodulation for methanol-induced retinal toxicity Proc Natl Acad Sci U S A 100 2003 3439 3444 (Pubitemid 36356602)
80. C. Moro, N. Torres, N. El Massri, D. Ratel, D.M. Johnstone, and J. Stone et al. Photobiomodulation preserves behaviour and midbrain dopaminergic cells from MPTP toxicity: evidence from two mouse strains BMC Neurosci 14 2013 40
81. L. Detaboada, S. Ilic, S. Leichliter-Martha, U. Oron, A. Oron, and J. Streeter Transcranial application of low-energy laser irradiation improves neurological deficits in rats following acute stroke Lasers Surg Med 38 2006 70 73 (Pubitemid 43238086)
82. P.A. Lapchak, J. Wei, and J.A. Zivin Transcranial infrared laser therapy improves clinical rating scores after embolic strokes in rabbits Stroke 35 2004 1985 1988 (Pubitemid 38971888)
83. F. Schiffer, A.L. Johnston, C. Ravichandran, A. Polcari, M.H. Teicher, and R.H. Webb et al. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety Behav Brain Funct 5 2009 46
84. D.W. Barrett, and F. Gonzalez-Lima Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans Neuroscience 230 2013 13 23
85. C.E. Stafstrom, and J.M. Rho The ketogenic diet as a treatment paradigm for diverse neurological disorders Front Pharmacol 3 2012 59
86. S.T. Henderson, J.L. Vogel, L.J. Barr, F. Garvin, J.J. Jones, and L.C. Costantini Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial Nutr Metab (Lond) 6 2009 31
87. O.E. Owen, A.P. Morgan, H.G. Kemp, J.M. Sullivan, M.G. Herrera, and G.F. Cahill Jr. Brain metabolism during fasting J Clin Invest 46 1967 1589 1595
88. Y. Zhang, Y. Kuang, K. Xu, D. Harris, Z. Lee, and J. LaManna et al. Ketosis proportionately spares glucose utilization in brain J Cereb Blood Flow Metab 33 2013 1307 1311
89. F. Pifferi, S. Tremblay, E. Croteau, M. Fortier, J. Tremblay-Mercier, and R. Lecomte et al. Mild experimental ketosis increases brain uptake of 11C-acetoacetate and 18F-fluorodeoxyglucose: a dual-tracer PET imaging study in rats Nutr Neurosci 14 2011 51 58
90. K.J. Bough, J. Wetherington, B. Hassel, J.F. Pare, J.W. Gawryluk, and J.G. Greene et al. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet Ann Neurol 60 2006 223 235 (Pubitemid 44182397)
91. H.S. Noh, H.P. Lee, D.W. Kim, S.S. Kang, G.J. Cho, and J.M. Rho et al. A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet Brain Res Mol Brain Res 129 2004 80 87 (Pubitemid 39304251)
92. M. Roy, S. Nugent, J. Tremblay-Mercier, S. Tremblay, A. Courchesne-Loyer, and J.F. Beaudoin et al. The ketogenic diet increases brain glucose and ketone uptake in aged rats: a dual tracer PET and volumetric MRI study Brain Res 1488 2012 14 23
93. M. Balietti, B. Giorgetti, G. Di Stefano, T. Casoli, D. Platano, and M. Solazzi et al. A ketogenic diet increases succinic dehydrogenase (SDH) activity and recovers age-related decrease in numeric density of SDH-positive mitochondria in cerebellar Purkinje cells of late-adult rats Micron 41 2010 143 148
94. S.G. Jarrett, J.B. Milder, L.P. Liang, and M. Patel The ketogenic diet increases mitochondrial glutathione levels J Neurochem 106 2008 1044 1051
95. J.B. Milder, L.P. Liang, and M. Patel Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet Neurobiol Dis 40 2010 238 244
96. T. Shimazu, M.D. Hirschey, J. Newman, W. He, K. Shirakawa, and N. Le Moan et al. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor Science 339 2013 211 214
97. P.G. Sullivan, N.A. Rippy, K. Dorenbos, R.C. Concepcion, A.K. Agarwal, and J.M. Rho The ketogenic diet increases mitochondrial uncoupling protein levels and activity Ann Neurol 55 2004 576 580 (Pubitemid 38391976)
98. H.E. Mohamed, S.E. El-Swefy, L.A. Rashed, and S.K. Abd El-Latif Biochemical effect of a ketogenic diet on the brains of obese adult rats J Clin Neurosci 17 2010 899 904
99. M. Balietti, B. Giorgetti, P. Fattoretti, Y. Grossi, G. Di Stefano, and T. Casoli et al. Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats Rejuvenation Res 11 2008 631 640 (Pubitemid 351931473)
100. T. Zarnowski, T. Choragiewicz, M. Tulidowicz-Bielak, S. Thaler, R. Rejdak, and I. Zarnowski et al. Ketogenic diet increases concentrations of kynurenic acid in discrete brain structures of young and adult rats J Neural Transm 119 2012 679 684
101. C. Klein, C. Patte-Mensah, O. Taleb, J.J. Bourguignon, M. Schmitt, and F. Bihel et al. The neuroprotector kynurenic acid increases neuronal cell survival through neprilysin induction Neuropharmacology 70 2013 254 260
102. I. Chmiel-Perzynska, R. Kloc, A. Perzynski, S. Rudzki, and E.M. Urbanska Novel aspect of ketone action: beta-hydroxybutyrate increases brain synthesis of kynurenic acid in vitro Neurotox Res 20 2011 40 50
103. A. Hallen, J.F. Jamie, and A.J. Cooper Lysine metabolism in mammalian brain: an update on the importance of recent discoveries Amino Acids 2013
104. K. Hensley, K. Venkova, and A. Christov Emerging biological importance of central nervous system lanthionines Molecules 15 2010 5581 5594
105. P. Bubber, V. Haroutunian, G. Fisch, J.P. Blass, and G.E. Gibson Mitochondrial abnormalities in Alzheimer brain: mechanistic implications Ann Neurol 57 2005 695 703 (Pubitemid 40628858)
106. G.E. Gibson, K.F. Sheu, J.P. Blass, A. Baker, K.C. Carlson, and B. Harding et al. Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease Arch Neurol 45 1988 836 840
107. I. Maurer, S. Zierz, and H.J. Moller A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients Neurobiol Aging 21 2000 455 462 (Pubitemid 30349116)
108. F. Bosetti, F. Brizzi, S. Barogi, M. Mancuso, G. Siciliano, and E.A. Tendi et al. Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease Neurobiol Aging 23 2002 371 376 (Pubitemid 34312019)
109. S.M. Cardoso, M.T. Proenca, S. Santos, I. Santana, and C.R. Oliveira Cytochrome c oxidase is decreased in Alzheimer's disease platelets Neurobiol Aging 25 2004 105 110 (Pubitemid 37522198)
110. W.D. Parker Jr., J. Parks, C.M. Filley, and B.K. Kleinschmidt-DeMasters Electron transport chain defects in Alzheimer's disease brain Neurology 44 1994 1090 1096 (Pubitemid 24188184)
111. E. Aso, J. Semakova, L. Joda, V. Semak, L. Halbaut, and A. Calpena et al. Triheptanoin supplementation to ketogenic diet curbs cognitive impairment in APP/PS1 mice used as a model of familial Alzheimer's disease Curr Alzheimer Res 10 2013 290 297
112. S.T. Henderson, and J. Poirier Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study BMC Med Genet 12 2011 137
113. R. Krikorian, M.D. Shidler, K. Dangelo, S.C. Couch, S.C. Benoit, and D.J. Clegg Dietary ketosis enhances memory in mild cognitive impairment Neurobiol Aging 33 2012 425e19 425e27
114. M.A. Reger, S.T. Henderson, C. Hale, B. Cholerton, L.D. Baker, and G.S. Watson et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults Neurobiol Aging 25 2004 311 314 (Pubitemid 38220966)
115. Y. Kashiwaya, C. Bergman, J.H. Lee, R. Wan, M.T. King, and M.R. Mughal et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease Neurobiol Aging 34 2013 1530 1539
116. J. Zhang, Q. Cao, S. Li, X. Lu, Y. Zhao, and J.S. Guan et al. 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism Biomaterials 34 2013 7552 7562
117. C.M. Studzinski, W.A. MacKay, T.L. Beckett, S.T. Henderson, M.P. Murphy, and P.G. Sullivan et al. Induction of ketosis may improve mitochondrial function and decrease steady-state amyloid-beta precursor protein (APP) levels in the aged dog Brain Res 1226 2008 209 217
118. M. Zilberter, A. Ivanov, S. Ziyatdinova, M. Mukhtarov, A. Malkov, and A. Alpar et al. Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer's disease J Neurochem 125 2013 157 171
119. I. Van der Auwera, S. Wera, F. Van Leuven, and S.T. Henderson A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease Nutr Metab (Lond) 2 2005 28
120. T.L. Beckett, C.M. Studzinski, J.N. Keller, M. Paul Murphy, and D.M. Niedowicz A ketogenic diet improves motor performance but does not affect beta-amyloid levels in a mouse model of Alzheimer's disease Brain Res 1505 2013 61 67
121. M.L. Brownlow, L. Benner, D. D'Agostino, M.N. Gordon, and D. Morgan Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology PLoS ONE 8 2013 e75713
122. T.B. VanItallie, C. Nonas, A. Di Rocco, K. Boyar, K. Hyams, and B. Heymsfield Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study Neurology 64 2005 728 730 (Pubitemid 40261909)
123. Z. Zhao, D.J. Lange, A. Voustianiouk, D. MacGrogan, L. Ho, and J. Suh et al. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis BMC Neurosci 7 2006 29
124. W. Zhao, M. Varghese, P. Vempati, A. Dzhun, A. Cheng, and J. Wang et al. Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease PLoS ONE 7 2012 e49191
125. D.N. Ruskin, J.L. Ross, M. Kawamura Jr., T.L. Ruiz, J.D. Geiger, and S.A. Masino A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington's disease Physiol Behav 103 2011 501 507
126. S. Lim, A.S. Chesser, J.C. Grima, P.M. Rappold, D. Blum, and S. Przedborski et al. d-beta-Hydroxybutyrate is protective in mouse models of Huntington's disease PLoS ONE 6 2011 e24620
127. B. Cheng, X. Yang, L. An, B. Gao, X. Liu, and S. Liu Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease Brain Res 1286 2009 25 31
128. K. Tieu, C. Perier, C. Caspersen, P. Teismann, D.C. Wu, and S.D. Yan et al. d-beta-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease J Clin Invest 112 2003 892 901 (Pubitemid 38063747)
129. K.S. Appelberg, D.A. Hovda, and M.L. Prins The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat J Neurotrauma 26 2009 497 506
130. Y. Deng-Bryant, M.L. Prins, D.A. Hovda, and N.G. Harris Ketogenic diet prevents alterations in brain metabolism in young but not adult rats after traumatic brain injury J Neurotrauma 28 2011 1813 1825
131. M.L. Prins, S.M. Lee, L.S. Fujima, and D.A. Hovda Increased cerebral uptake and oxidation of exogenous betaHB improves ATP following traumatic brain injury in adult rats J Neurochem 90 2004 666 672 (Pubitemid 38989398)
132. M.L. Prins, and D.A. Hovda The effects of age and ketogenic diet on local cerebral metabolic rates of glucose after controlled cortical impact injury in rats J Neurotrauma 26 2009 1083 1093
133. Z.G. Hu, H.D. Wang, W. Jin, and H.X. Yin Ketogenic diet reduces cytochrome c release and cellular apoptosis following traumatic brain injury in juvenile rats Ann Clin Lab Sci 39 2009 76 83
134. Z.G. Hu, H.D. Wang, L. Qiao, W. Yan, Q.F. Tan, and H.X. Yin The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats Brain Inj 23 2009 459 465
135. M. Suzuki, M. Suzuki, K. Sato, S. Dohi, T. Sato, and A. Matsuura et al. Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats Jpn J Pharmacol 87 2001 143 150
136. Y. Kim do, J. Hao, R. Liu, G. Turner, F.D. Shi, and J.M. Rho Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis PLoS ONE 7 2012 e35476
137. L. Massieu, M.L. Haces, T. Montiel, and K. Hernandez-Fonseca Acetoacetate protects hippocampal neurons against glutamate-mediated neuronal damage during glycolysis inhibition Neuroscience 120 2003 365 378 (Pubitemid 37288773)
138. J. Mejia-Toiber, T. Montiel, and L. Massieu d-beta-Hydroxybutyrate prevents glutamate-mediated lipoperoxidation and neuronal damage elicited during glycolysis inhibition in vivo Neurochem Res 31 2006 1399 1408 (Pubitemid 44900579)
139. M.A. Puchowicz, J.L. Zechel, J. Valerio, D.S. Emancipator, K. Xu, and S. Pundik et al. Neuroprotection in diet-induced ketotic rat brain after focal ischemia J Cereb Blood Flow Metab 28 2008 1907 1916
140. M. Suzuki, M. Suzuki, Y. Kitamura, S. Mori, K. Sato, and S. Dohi et al. Beta-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia Jpn J Pharmacol 89 2002 36 43 (Pubitemid 34618607)
141. K.K. Tai, N. Nguyen, L. Pham, and D.D. Truong Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration J Neural Transm 115 2008 1011 1017
142. K.K. Tai, and D.D. Truong Ketogenic diet prevents seizure and reduces myoclonic jerks in rats with cardiac arrest-induced cerebral hypoxia Neurosci Lett 425 2007 34 38 (Pubitemid 47410357)